Perinatal HIV infection is associated with deficits in muscle function in children and adolescents in Zimbabwe.

OBJECTIVES: To determine how muscle strength, power, mass, and density (i.e. quality) differ between children living with HIV (CWH) and those uninfected, and whether antiretroviral therapy (ART) regime is associated with muscle quality. DESIGN: A cross-sectional study in Harare, Zimbabwe. METHODS: The study recruited CWH aged 8-16 years, taking ART for at least 2 years, from HIV clinics, and HIV-uninfected children from local schools. Muscle outcomes comprised grip strength measured by hand-held Jamar dynamometer, lower limb power measured by standing long-jump distance, lean mass measured by dual-energy X-ray absorptiometry, and muscle density (reflecting intramuscular fat) by peripheral quantitative computed tomography. Linear regression calculated adjusted mean differences (aMD) by HIV status. RESULTS: Overall, 303 CWH and 306 without HIV, had mean (SD) age 12.5 (2.5) years, BMI 17.5 (2.8), with 50% girls. Height and fat mass were lower in CWH, mean differences (SE) 7.4 (1.1) cm and 2.7 (0.4)kgs, respectively. Male CWH had lower grip strength [aMD 2.5 (1.1-3.9) kg, P  < 0.001], long-jump distance [7.1 (1.8-12.5) cm, P  = 0.006], muscle density [0.58 (0.12-1.05) mg/cm 3 , P  = 0.018, but not lean mass 0.06 (-1.08 to 1.21) kg, P  = 0.891) versus boys without HIV; differences were consistent but smaller in girls. Mediation analysis suggested the negative effect of HIV on jumping power in boys was partially mediated by muscle density ( P  = 0.032). CWH taking tenofovir disoproxil fumarate (TDF) had lower muscle density [0.56 (0.00-1.13)mg/cm 3 , P  = 0.049] independent of fat mass, than CWH on other ART. CONCLUSION: Perinatally acquired HIV is associated, particularly in male individuals, with reduced upper and lower limb muscle function, not mass. Intra-muscular fat (poorer muscle quality) partially explained reductions in lower limb function. TDF is a novel risk factor for impaired muscle quality.

Pandemic preparedness and responsiveness of research review committees: lessons from review of COVID-19 protocols at KEMRI Wellcome Trust Research Programme in Kenya.

Background: The scale of the COVID-19 pandemic and novelty of SARS-CoV-2 presented unprecedented challenges in the review of COVID-19 protocols. We investigated how research at the Kenya Medical Research Institute - Wellcome Trust Research Programme (KWTRP) was reviewed, including by institutional and national level committees. Methods: A document review and in-depth interviews with researchers, regulators and research reviewers were conducted. Documents reviewed included research logs of all protocols submitted between April-1-2020 and March-31-2021, feedback letters from review committees for 10 new COVID-19 protocols (n=42), and minutes from 35 COVID-19 research review meetings. Fifteen in-depth interviews were conducted with respondents purposively selected because of their experience of developing or reviewing COVID-19 protocols at the institution level (n=9 researchers, engagement officers and regulators) or their experience in reviewing proposals at a national-level (n=6 committee members). Data were managed and analyzed using MS Excel and NVivo12. Results: Between April-1-2020 and March-31-2021, 30 COVID-19-related submissions by KWTRP researchers were approved. Changes to the review system included strengthening the online system for protocol submission and review, recruiting more reviewers, and trialing a joint review process. The turnaround time from submission to national approval/rejection over this period was faster than pre-pandemic, but slower than the national committee's target. COVID-19-specific ethics questions centred on: virtual informed consent and data collection; COVID-19 prevention, screening and testing procedures; and the challenges of study design and community engagement during the pandemic. Conclusions: The unprecedented challenges of the pandemic and added bureaucratic requirements created a more complex review process and delayed final approval of research protocols. The feasibility of conducting joint review of research during public health emergencies in Kenya needs further investigation. Consideration of the unique COVID-19 ethics issues raised in this paper might aid expedience in current and future reviews.